DK2783692T3 - Tumorsuppression under anvendelse af humant placenta-perfusat og humane placenta-afledte intermediære naturlige dræberceller - Google Patents

Tumorsuppression under anvendelse af humant placenta-perfusat og humane placenta-afledte intermediære naturlige dræberceller Download PDF

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DK2783692T3
DK2783692T3 DK13188706.9T DK13188706T DK2783692T3 DK 2783692 T3 DK2783692 T3 DK 2783692T3 DK 13188706 T DK13188706 T DK 13188706T DK 2783692 T3 DK2783692 T3 DK 2783692T3
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natural killer
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Xiaokui Zhang
Vanessa A Voskinarian-Berse
Lin Kang
Neerav Dilip Padlina
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Celularity Inc
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Claims (15)

1. Sammensætning omfattende isolerede CD56+, CD16' placentale intermediære naturlige dræberceller, hvor de CD56+, CD16' placentale intermediære naturlige dræberceller isoleres fra placenta-perfusat, og hvor de CD56+, CD16' placentale intermediære naturlige dræberceller omfatter mindst 50% celler i sammensætningen.
2. Sammensætning ifølge krav 1, hvor de CD56+, CD16' placentale intermediære naturlige dræberceller udtrykker et eller flere af microRNA'erne hsa-miR-100, hsa-miR-127, hsa-miR-211, hsa-miR-302c, hsa-miR-326, hsa-miR-337, hsa-miR-497, hsa-miR-512-3p, hsa-miR-515-Sp, hsa-miR-517b, hsa-miR-517c, hsa-miR-518a, hsa-miR-518e, hsa-miR-519d, hsa-miR-520g, hsa-miR-520h, hsa-miR-564, hsa-miR-566, hsa-miR-618, eller hsa-miR-99a ved et detekterbart højere niveau end naturlige naturlige dræberceller fra perifert blod.
3. Sammensætning ifølge krav 1 eller 2, hvor de CD56+, CD16‘ placentale intermediære naturlige dræberceller udtrykker et eller flere af aminopeptidase N protein, apolipoprotein E protein, atrophin-1 interagerende protein 1, innexin inx-3 protein, integrin alpha-2 precursorprotein, integrin beta-5 precursor, mastcelleoverflade-glycoprotein GP49B precursorprotein, eller ryanodinreceptor 1 protein; og hvor CD56+, CD16' cellerne ikke udtrykker et eller flere af fibroblastvækstfaktorreceptor 4 precursorprotein, immunitet-forbundet nukleotid 4-lignende protein, integrin alpha-L precursorprotein, integrin beta 2 precursorprotein, integrin beta 4 precursorprotein, membran-bundet lytisk murein transglycosylase D precursorprotein, oxysterolbindingsprotein-relateret protein 8 eller perforin 1 precursorprotein.
4. Sammensætning ifølge et hvilket som helst af kravene 1 til 3, hvor sammensætningen omfatter mindst ca. 80% CD56+, CD16- placentale intermediære naturlige dræberceller, eller mindst ca. 95% CD56+, CD16-placentale intermediære naturlige dræberceller.
5. Sammensætning ifølge et hvilket som helst af kravene 1 til 4, hvor de CD56+, CD16' placentale intermediære naturlige dræberceller er fra et enkelt individ.
6. Sammensætning ifølge et hvilket som helst af kravene 1 til 5, hvor de placentale intermediære naturlige dræberceller har været bragt i kontakt med en immunomodulatorisk forbindelse i en mængde og i et tidsrum, der er tilstrækkeligt for de placentale intermediære naturlige dræberceller til at udtrykke detekterbart mere granzym B end et tilsvarende antal af placentale intermediære naturlige dræberceller, som ikke har været bragt i kontakt med den immunomodulatoriske forbindelse, hvor den immunomodulatoriske forbindelse er pomalidomid eller lenalidomid.
7. Sammensætning ifølge et hvilket som helst af kravene 1 til 5, hvor de placentale intermediære naturlige dræberceller har været bragt i kontakt med en immunomodulatorisk forbindelse i en mængde og i et tidsrum, der er tilstrækkeligt for de placentale intermediære naturlige dræberceller til at udvise detekterbart mere cytotoksicitet mod tumorceller end et tilsvarende antal af placentale intermediære naturlige dræberceller, som ikke har været bragt i kontakt med den immunomodulatoriske forbindelse.
8. Sammensætning ifølge krav 6 eller 7, hvor de placentale intermediære naturlige dræberceller udtrykker en eller flere af BAX, CCL5, CD68, CD8A, CSF2, FAS, GUSB eller IL2RA på et højere niveau end et tilsvarende antal af placentale intermediære naturlige dræberceller, som ikke har været bragt i kontakt med den immunomodulatoriske forbindelse.
9. Sammensætning ifølge krav 6 eller 7, hvor de placentale intermediære naturlige dræberceller udtrykker en eller flere af BAX, CCL2, CCL3, CCL5, CSF1, CSF2, ECE1, FAS, GNLY, GUSB, GZMB, ILIA, IL2RA, IL8, IL10, LTA, PRF1, PTGS2, SKI, eller TBX21 på et højere niveau end et tilsvarende antal af placentale intermediære naturlige dræberceller, som ikke har været bragt i kontakt med den immunomodulatoriske forbindelse.
10. Sammensætning ifølge et hvilket som helst af kravene 1 til 9, hvor sammensætningen endvidere omfatter isoleret CD56+, CD16+ naturlige dræberceller.
11. Sammensætning ifølge krav 10, hvor de CD56+, CD16+ naturlige dræberceller er fra et andet individ en de CD56+, CD16' placentale intermediære naturlige dræberceller.
12. Sammensætning ifølge krav 10, hvor de CD56+, CD16' placentale intermediære naturlige dræberceller og de CD56+, CD16+ naturlige dræberceller er fra et enkelt individ.
13. Sammensætning ifølge et hvilket som helst af kravene 1 til 9, hvor sammensætningen endvidere omfatter naturlige dræberceller isoleret fra navlestrengsblod, hvor navlestrengsblodet er isoleret fra placentaen, fra hvilken placenta-perfusatet er opnået.
14. Sammensætning ifølge krav 13, hvor de CD56+, CD16' placentale intermediære naturlige dræberceller er kombineret med de naturlige dræberceller isoleret fra navlestrengsblod (i) i et forhold på 50 CD56+, CD16' placentale intermediære naturlige dræberceller til 50 naturlige dræberceller isoleret fra navlestrengsblod (ii) i et forhold på 55 CD56+, CD16' placentale intermediære naturlige dræberceller til 45 naturlige dræberceller isoleret fra navlestrengsblod (iii) i et forhold på 60 CD56+, CD16' placentale intermediære naturlige dræberceller til 40 naturlige dræberceller isoleret fra navlestrengsblod (iv) i et forhold på 65 CD56+, CD16' placentale intermediære naturlige dræberceller til 35 naturlige dræberceller isoleret fra navlestrengsblod (v) i et forhold på 70 CD56+, CD16' placentale intermediære naturlige dræberceller til 30 naturlige dræberceller isoleret fra navlestrengsblod (vi) i et forhold på 75 CD56+, CD16' placentale intermediære naturlige dræberceller til 25 naturlige dræberceller isoleret fra navlestrengsblod (vii) i et forhold på 80 CD56+, CD16' placentale intermediære naturlige dræberceller til 20 naturlige dræberceller isoleret fra navlestrengsblod (viii) i et forhold på 85 CD56+, CD16' placentale intermediære naturlige dræberceller til 15 naturlige dræberceller isoleret fra navlestrengsblod (ix) i et forhold på 90 CD56+, CD16' placentale intermediære naturlige dræberceller til 10 naturlige dræberceller isoleret fra navlestrengsblod (x) i et forhold på 95 CD56+, CD16' placentale intermediære naturlige dræberceller til 5 naturlige dræberceller isoleret fra navlestrengsblod eller (xi) i et forhold på 100 CD56+, CD16' placentale intermediære naturlige dræberceller til 1 naturlig dræbercelle isoleret fra navlestrengsblod.
15. Sammensætning ifølge krav 14, hvor de kombinerede naturlige dræberceller omfatter: (i) et detekterbart højere antal CD3'CD56+CD16' naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod; (ii) et detekterbart lavere antal CD3'CD56+CD16+ naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod; (iii) et detekterbart højere antal CD3OD56+KIR2DL2/L3+ naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod; (iv) et detekterbart lavere antal CD3'CD56+NKp46+ naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod; (v) et detekterbart højere antal CD3'CD56+NKp30+ naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod; (vi) et detekterbart højere antal CD3OD56+2B4+ naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod; eller (vii) et detekterbart højere antal CD3OD56+CD94+ naturlige dræberceller end et tilsvarende antal naturlige dræberceller fra perifert blod.
DK13188706.9T 2007-09-28 2008-09-29 Tumorsuppression under anvendelse af humant placenta-perfusat og humane placenta-afledte intermediære naturlige dræberceller DK2783692T3 (da)

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DK13188706.9T DK2783692T3 (da) 2007-09-28 2008-09-29 Tumorsuppression under anvendelse af humant placenta-perfusat og humane placenta-afledte intermediære naturlige dræberceller

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CN (3) CN101878034B (da)
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